Transforming Growth Factor-β Regulates Stearoyl Coenzyme A Desaturase Expression through a Smad Signaling Pathway

Samuel, William; Nagineni, Chandrasekharam N.; Kutty, R. Krishnan; Parks, W. Tony; Gordon, Joel S.; Prouty, Stephen M.; Hooks, John J.; Wiggert, Barbara

doi:10.1074/jbc.m108730200

Cited by 37 publications

(33 citation statements)

References 70 publications

(66 reference statements)

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“…Our finding that increasing ∆9-desaturase mRNA concentrations are higher than the corresponding ∆9-desaturase enzyme activities are well in line with previous results [32,33]. The differences could be explained by the fact that the half-life of ∆9-desaturase is very short [32] thus rapid changes of mRNA levels are not equivalently translated into a corresponding increase in ∆9-desaturase enzyme activity.…”

Section: Discussionsupporting

confidence: 91%

Glucose oversupply increases Δ9-desaturase expression and its metabolites in rat skeletal muscle

et al. 2003

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Aim/hypothesis. Previous studies have shown that prolonged glucose infusion causes insulin resistance and triglyceride accumulation in rat skeletal muscle. In this study, we investigated a possible relationship between insulin resistance and the composition of different accumulated lipid fractions in rat skeletal muscle. Methods. Continuous glucose infusion was carried out in rats for 7 days. Lipids were extracted from skeletal muscle, separated by thin layer chromatography and fatty acid composition of phospholipids, triglycerides, diglycerides, free fatty acids and cholesterol esters fractions was analysed by gas chromatography. ∆9-Desaturase mRNA was measured by real time polymerase chain reaction. The enzyme activity was measured in the microsomal fractions. Results. Prolonged glucose infusion (5 days) increased the relative content of palmitoleic acid (16:1 N7) several-fold (2.3-to 5.8-fold) in four out of five lipid fractions and enhanced oleic acid (18:1 N9) two-fold in three lipid fractions suggesting increased ∆9-desaturase activity while the content of several polyunsaturated fatty acids was reduced. In parallel, ∆9-Desaturase mRNA contents and enzyme activities in skeletal muscle were increased 10-fold, 75-fold, 2.6-fold and 7.7-fold after 2 and 5 days of glucose infusion, respectively. Conclusion/interpretation. Our results suggest that long-term glucose oversupply induces a rapid increase in ∆9-desaturase expression and enzyme activity in skeletal muscle which leads to fast and specific changes in fatty acid metabolism possibly contributing to the insulin resistance in this animal model. [Diabetologia (2003) 46:203-212]

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Section: Discussionsupporting

confidence: 91%

Glucose oversupply increases Δ9-desaturase expression and its metabolites in rat skeletal muscle

et al. 2003

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“…More interestingly, it was also observed that the expression of SCD, SMAD3 and CYB5R3 was lower in the mammary gland of Defective genotype goats (Table 1). SMAD3 encodes a protein that belongs to a large family known as cytoplasmic mediators, which regulate the transcription of target genes (Heldin et al, 1997), including the SCD gene (Samuel et al, 2002). Moreover, stearoyl-CoA desaturase (encoded by the SCD gene) and NADHcytochrome b5 reductase (encoded by the CYB5R3 gene) are components of a FA-desaturase system directing the synthesis of D-9 unsaturated FA.…”

Section: Resultsmentioning

confidence: 99%

Goat’s αS1-casein polymorphism affects gene expression profile of lactating mammary gland

Ollier

Chauvet

Martin³

et al. 2008

Animal

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Goat's a S1 -casein (CSN1S1) polymorphism has a significant effect on milk protein and lipid composition, which affects the nutritional quality and technological properties of milk. Moreover, this polymorphism has a large impact on the morphology of mammary epithelial cells. To explore the metabolic pathways modulated in relation to this polymorphism, we compared the mammary gene expression profiles of two groups of lactating goats carrying either two reference or two defective alleles, using a bovine oligonucleotide microarray representing 8379 genes. We identified 41 differentially expressed genes between the two genotype groups. In particular, we showed a downregulation of two key lipogenic genes encoding fatty acid synthase and glycerol-3-phosphate acyltransferase in agreement with the low fat concentration associated with CSN1S1 deficiency. In addition, this study highlights changes in the expression level of several genes known to influence membrane fluidity, cell-cell interaction or chromatin organization. Our results open up new fields of investigation on structural modifications associated with CSN1S1 deficiency that could affect mammary gland function.

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“…Interestingly, TGFBI was also found to be overexpressed in lung cancer and was correlated with later stages of lung cancer (Sasaki et al, 2002). SCD can be induced by TGF-b1, 2 or 3 in cultured human retinal pigment epithelial cells (Samuel et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Bone morphogenetic protein 3B silencing in non-small-cell lung cancer

et al. 2004

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Bone morphogenetic protein 3B (BMP3B) is a member of the TGF-b superfamily. The BMP3B promoter sequence was previously identified as a target for aberrant DNA methylation in non-small-cell lung cancer (NSCLC). Aberrant DNA hypermethylation in the BMP3B promoter is associated with downregulation of BMP3B transcription in both primary human lung cancers as well as lung cancer cell lines. In order to understand the mechanisms of BMP3B silencing in lung cancer, a sample set of 91 primary NSCLCs was used to detect aberrant BMP3B promoter methylation, mutations in the coding sequence of BMP3B, and loss of heterozygosity (LOH). Our results showed that 45 of 91 (or 49.5%) tested primary NSCLCs exhibited increased promoter methylation, and 40% demonstrated LOH in at least one of the flanking microsatellite markers sJRH and D10S196 (63 kb upstream or 3.338 Mbp downstream of BMP3B). The lung cancer cell line A549, a type II alveolar epithelial human lung cancer cell line, is characterized by aberrant DNA promoter methylation. We used retroviral vector constructs containing the BMP3B cDNA to re-express the gene in A549 cells and to investigate the effects on cell growth. No change in the cell growth rate was observed after BMP3B re-expression, as compared to the vector controls. Although the number of colonies formed in anchorage-dependent assays was only slightly decreased, the colony-forming ability of A549 cells after BMP3B expression in anchorage-independent assays in soft agar was significantly reduced to 10% (Po0.005, t-test). Moreover, the in vivo tumorigenicity assay in nude mice indicated that cells re-expressing BMP3B grew significantly slower than cells not expressing BMP3B (Po0.05, t-test). In conclusion, this study provides evidence that BMP3B expression is repressed by different mechanisms in lung cancer, and that the silencing of BMP3B promotes lung tumor development.

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Transforming Growth Factor-β Regulates Stearoyl Coenzyme A Desaturase Expression through a Smad Signaling Pathway

Cited by 37 publications

References 70 publications

Glucose oversupply increases Δ9-desaturase expression and its metabolites in rat skeletal muscle

Glucose oversupply increases Δ9-desaturase expression and its metabolites in rat skeletal muscle

Goat’s αS1-casein polymorphism affects gene expression profile of lactating mammary gland

Bone morphogenetic protein 3B silencing in non-small-cell lung cancer

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